Inside Health

History Counsels Caution on Diet Pills

By DENISE GRADY

Published: May 25, 1999

The weight-loss drug Xenical, approved last month, had barely reached the market when Web sites selling the drug sprang up to tap into the intense consumer demand that accompanies the debut of anything marketed to make people lose weight.

But in their eagerness for pills to help them slim down, people may conveniently overlook something that doctors remember all too well: weight-loss drugs in general have have a rather alarming history.

''There is a very checkered past,'' said Dr. Steven Heymsfield, deputy director of the obesity research center at St. Luke's Roosevelt Hospital in Manhattan. Although Dr. Heymsfield does prescribe weight-loss medications for some of his patients, he said: ''I believe we should use these drugs judiciously. If you forget the past you're doomed, right?''

Two years ago, the popular drug combination known as fen-phen was blamed for damaged heart valves, and two drugs that had been part of it were taken off the market. (A third, the appetite suppressant phentermine, is still available.)

During the 1930's, about 100,000 Americans took a chemical, dinitrophenol, which prevented food energy from being turned into fat. ''The energy is just liberated as heat,'' Dr. Heymsfield said. ''You sort of become a firefly.''

Unfortunately, dinitrophenol was poisonous, causing blindness and even death.

''In days gone by, thyroid hormone was very common,'' said Dr. Jules Hirsch, an obesity expert and senior physician at the Rockefeller University Hospital in Manhattan. It increased metabolism, and made people lose weight. But the excess hormone disrupted heart rhythm and caused muscle weakness. ''It became discredited, as it should have been,'' Dr. Hirsch said.

Dr. Albert Stunkard, director emeritus of the weight and eating disorders program at the University of Pennsylvania, said, ''The first drugs that were used that turned out to be effective were amphetamines.'' These stimulants, introduced in the 1950's, suppressed appetite and may have raised metabolism.

''They were used, and then abused,'' Dr. Stunkard said. ''But they're actually very effective, and you can lose a lot of weight. Long, continued use had bad effects, however, like making people paranoid. And when they stopped, they became depressed and regained the weight. Congressional hearings on amphetamine abuse were held in the 1960's, and after that you weren't allowed to use them for weight loss.''

One of the strangest weight loss crazes was human chorionic gonadotropin, a hormone produced by pregnant women. During the 1960's, injections of the hormone were said to stimulate rapid weight loss -- if they were combined with a strict, low-fat, low-calorie diet. Some patients were also told that if they cheated on the diet, the hormone would actually cause rapid weight gain.

''It was a scam,'' said Dr. Heymsfield.

In the wake of past debacles, he said, weight loss drugs are studied longer and tested more carefully, and doctors tend to have more confidence in them. The only ones on the market besides phentermine are Xenical and Meridia.

Xenical, also called orlistat, blocks the intestine from absorbing about 30 percent of the fat that a person eats, and studies have shown that people who take it may lose from 5 percent to 10 percent of their body weight in a year. Meridia, or sibutramine, is an appetite suppressant approved in 1996. Both drugs are supposed to be used along with a reduced-calorie diet, and only by people who meet the technical definition of obese, meaning that they weigh 30 percent more than they should, or 20 percent more, with complications like diabetes or high blood pressure.

Both drugs have side effects. Meridia can raise blood pressure, and Xenical can cause diarrhea or even fecal incontinence if a person eats too much fat while taking it.

But people still clamor for them, and Dr. Heymsfield said he prescribes them if he cannot talk a patient out of the idea, or if diet and exercise have simply not worked.

''They do help people under certain circumstances,'' he said. But, he emphasized, the drugs do not work well without diet and exercise, and researchers do not know whether people who are helped by them will be able to keep the weight off in the long run.

Photo: The approval last month of Xenical was met by intense demand from consumers.